Aims: We aimed to evaluate relationship between YKL-40 and endothelial dysfunction in chronic kidney disease. Patients/methods: Twenty-nine hemodialysis patients, 101 patients with non-dialytic (stage 2, 3, 4, 5ND) chronic kidney disease (CKD) and 38 healthy individuals as a control group were included. YKL-40 levels were measured with ELISA. Endothelial dysfunction was indirectly measured with Flow-mediated dilatation percentage (FMD) in the brachial artery. Results: YKL-40 levels were higher in CKD patients than controls and highest in HD patients (p=.001). Adversely FMD values were lower in non-dialytic CKD patients and lowest in HD patients (p=.001). YKL-40 negatively correlated with eGFR and FMD values (r=-0,674 and r=-0,471 respectively). Conclusion: This study shows that YKL-40 increases with CKD stage and is negatively correlated with FMD measurements.
Background: Despite improved survival outcomes with immune checkpoint inhibitors (ICIs), the treatment response of patients with metastatic melanoma remains highly variable. There is a growing need for reliable, accessible prognostic tools that incorporate clinical and inflammatory markers in order to stratify patients better and guide therapeutic decisions. Methods: We conducted a retrospective cohort study involving 73 patients with metastatic cutaneous melanoma treated with ICIs at a single tertiary center between 2017 and 2024. Baseline clinical and laboratory parameters were collected to calculate the Royal Marsden Hospital (RMH), Gustave Roussy Immune (GRIm) and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) and progression-free survival (PFS) were analyzed via Kaplan–Meier estimates and Cox proportional hazards models. Prognostic performance was assessed using Harrell’s concordance index (C-index) and receiver operating characteristic (ROC) analysis. Results: The median follow-up was 35.9 months, and the median OS was 22.1 months. All three scores were significantly associated with OS in univariate analysis. In multivariate models, only the RMH (HR: 5.45, p < 0.001) and MDA-ICI (HR: 4.24, p = 0.015) scores remained independent predictors of OS. Harrell’s C-index indicated strong discriminative ability for both RMH (0.742) and MDA-ICI (0.730) scores, whereas the GRIm score demonstrated lower predictive accuracy (0.615). Similarly, ROC curve analysis showed higher AUC values for RMH (0.732) and MDA-ICI (0.739) compared with GRIm (0.595). Conclusions: In this real-world cohort of metastatic melanoma patients treated with ICI, the RMH and MDA-ICI scores demonstrated favorable prognostic performance and outperformed the GRIm score in predicting overall survival. These findings support the clinical utility of RMH and MDA-ICI as practical, accessible tools for prognostic risk stratification in melanoma, though external validation in larger, multicenter cohorts is required.
Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.
Background/Objectives: Metastatic testicular germ cell tumor (mGCT) is a highly curable disease with first-line cisplatin-based combination chemotherapy. This study aims to evaluate the clinicopathological characteristics and survival outcomes of patients with metastatic testicular cancer in a nationwide multicenter cohort. Methods: This multicenter retrospective cohort study included 316 male patients diagnosed with mGCT who were treated with first-line cisplatin-based chemotherapy across 10 institutions in Turkey between 2011 and 2024. Clinical and pathological data, including International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, treatment details, and survival outcomes, were analyzed. Results: The median age of the cohort was 28 years, and 76.3% of patients were diagnosed with non-seminoma. According to IGCCCG risk stratification, 53.2% had good-risk, 25.3% intermediate-risk, and 21.5% poor-risk disease. Median follow-up was 38.4 months. Among patients with seminoma, the 5-year overall survival (OS) rate was 100% in the good-risk group and 87.5% in the intermediate-risk group. In patients with non-seminoma, 5-year OS rates were 96.6%, 86.9%, and 65.1% in the good-, intermediate-, and poor-risk groups, respectively. Among 125 patients who received salvage treatment, high-dose chemotherapy (HDCT) significantly improved survival in the International Prognostic Factors Study Group (IPFSG) very high-risk group (3-year OS: 55.0% vs. 16.3% with conventional-dose chemotherapy (CDCT), p = 0.007). Conclusions: This study provides the first large-scale nationwide dataset on mGCT outcomes in Turkey, demonstrating overall survival rates comparable to international cohorts. The findings emphasize the importance of a multidisciplinary approach, adherence to treatment guidelines, and optimal surgical interventions in improving patient outcomes.
Background and Objectives: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for resectable gastric and gastroesophageal junction adenocarcinoma; however, up to 50% of patients develop metastatic recurrence. These patients have prior exposure to platinum and taxane agents, and optimal first-line treatment in the metastatic setting remains undefined. This study aimed to characterize real-world treatment patterns and outcomes in patients progressing after perioperative FLOT, focusing on relapse timing and HER2 status. Materials and Methods: This retrospective, multicenter cohort study included 296 patients from 31 centers across Türkiye, stratified into early relapse (≤6 months, n = 114) and late relapse (>6 months, n = 182) groups. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS for the entire cohort were 6 and 9 months, respectively. Early relapsers had significantly shorter median PFS (4 vs. 6 months, p = 0.029) and OS (8 vs. 12 months, p = 0.047); however, early relapse timing did not retain independent prognostic significance on multivariable analysis. No significant difference in PFS or OS was observed between cytotoxic chemotherapy regimens in either relapse group. HER2 positivity was the only independent predictor of improved PFS on multivariable Cox analysis (HR 0.48, 95% CI 0.29–0.81; p = 0.006). In the late relapse group, trastuzumab-based chemotherapy achieved a median PFS of 14 months and OS of 18 months, significantly superior to all cytotoxic regimens (PFS p = 0.007; OS p = 0.029). Conclusions: In patients progressing after perioperative FLOT, cytotoxic chemotherapy regimen selection did not demonstrate a statistically significant survival difference in this retrospective cohort, regardless of relapse timing. HER2 positivity is the dominant predictive biomarker, and trastuzumab-based therapy suggests a potential survival benefit that warrants prospective validation. Comprehensive biomarker profiling at metastatic diagnosis and prospective trials designed for this post-FLOT population are needed to establish evidence-based treatment standards.
Background: Achieving no evidence of disease (NED) in HER2-positive metastatic breast cancer (MBC) has been proposed as a response-state marker for durable disease control. However, its clinical significance and predictive factors are not yet well established. Methods: In this multicenter retrospective study at 13 oncology centers in Turkey, we analyzed 118 patients with stage IV HER2-positive MBC who received trastuzumab-based first-line therapy and remained progression-free for at least 36 months. Patients were stratified by radiologically defined NED status according to RECIST v1.1. Clinicopathological features were compared between groups, and predictors of NED were identified using logistic regression. Progression-free survival (PFS) was estimated by Kaplan–Meier analysis and assessed with Cox regression. Results: Of the 118 patients, 55 (46.6%) achieved NED. Compared with patients who did not achieve NED, those attaining NED were younger (median 46 vs. 53 years, p = 0.013), had better ECOG performance status (p = 0.005), were more likely to have HER2 IHC 3+ status (p = 0.015), and higher histologic grade tumors (p = 0.013). In multivariable logistic regression, ECOG PS 0 (vs. 1 ; OR = 5.99, p = 0.005), HER2 IHC 3+ (vs. IHC 2+/ISH+; OR = 4.79, p = 0.035), and histologic grade ≤2 (vs. grade 3 ; OR = 0.25, p = 0.011) were independently associated with NED attainment. Patients who achieved NED had experienced significantly longer PFS than those who did not (median 131 months vs. 66 months; p < 0.005). In multivariate Cox regression, NED remained independently associated with prolonged PFS (HR = 0.24, p = 0.003). Metastasis-directed local therapy and treatment regimen (trastuzumab vs. trastuzumab + pertuzumab) were not independently associated with NED attainment or PFS. Conclusions: In this multicenter cohort of pre-selected long-term responders, nearly half of HER2-positive MBC patients achieved radiologic NED. Radiologic NED was independently associated with prolonged PFS within this enriched population. Factors associated with NED attainment included favorable ECOG performance status, HER2 IHC 3+ expression, and high tumor grade; given the wide confidence intervals, these estimates should be interpreted cautiously as exploratory and hypothesis-generating.